Phosphatidylinositide (PI) 3-kinase binds to tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1) in insulin-treated adipocytes, and this step plays a central role in the regulated movement of the glucose transporter, GLUT4, from intracellular vesicles to the cell surface. PDGF, which also activates PI 3-kinase in adipocytes, has no significant effect on GLUT4 trafficking in these cells....

The k-Interval Routing Scheme (k-IRS) is a compact routing scheme on general networks. It has been studied extensively and recently been implemented on the latest generation of the INMOS transputer router chips. In this paper we investigate the time complexity of devising a minimal space k-IRS and we prove that the problem of deciding whether there exists a 2-IRS for any network G is NP-complet...

Nitric oxide (NO), which plays a role in the posttranslational modification of proteins, exhibits tumoricidal activity. However, the mechanism remains largely unclear. We investigated whether the regulation of insulin receptor substrate (IRS)-1 protein expression and insulin/insulin-like growth factor (IGF) signaling by NO is involved in the proliferation and invasion of pancreatic cancer cells...

ownload ic oxide (NO), which plays a role in the posttranslational modification of proteins, exhibits tumoricidal y. However, the mechanism remains largely unclear. We investigated whether the regulation of insulin resubstrate (IRS)-1 protein expression and insulin/insulin-like growth factor (IGF) signaling by NO is inin the proliferation and invasion of pancreatic cancer cells. NO donor inhibi...

The 60 kDa insulin receptor substrate in rat adipocytes that binds to the PI-3 kinase displays several functional characteristics in common with the IRS proteins; so we propose the name pp60(IRS3) to distinguish it from other tyrosine phosphorylated proteins of similar size. During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2. In mice lacking IRS-1, ...

OBJECTIVE To assess the relation of the metabolic insulin resistance syndrome (M-IRS) with coronary heart disease (CHD) in Pakistani patients. SUBJECTS 200 patients with angiographic disease (CHD(+)) matched with 200 patients with chest pain without occlusive disease (CHD(-)). DESIGN Prospective case-control study. SETTING Tertiary referral cardiology unit in Pakistan. RESULTS M-IRS was...

Insulin resistance is associated with cardiovascular disease. Impaired insulin receptor substrate (IRS)-mediated signal transduction is a major contributor to insulin resistance. Recently, IRS-1 phosphorylation at serine 307 by stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) has been highlighted as a molecular event that causes insulin resistance. We investigated IRS-1-mediat...

Serine and threonine phosphorylation of IRS-1 (insulin receptor substrate-1) has been reported to decrease its ability to be tyrosine-phosphorylated by the insulin receptor. Insulin itself may negatively regulate tyrosine phosphorylation of IRS-1 through a PI3K (phosphoinositide 3-kinase)-dependent feedback pathway. In the present study, we examined the regulation and role of IRS-1 serine phosp...

Glucose-6-phosphatase catalyzes the terminal step in the gluconeogenic and glycogenolytic pathways. In HepG2 cells, the maximum repression of basal glucose-6-phosphatase catalytic subunit (G6Pase) gene transcription by insulin requires two distinct promoter regions, designated A (located between -231 and -199) and B (located between -198 and -159), that together form an insulin response unit. R...

Insulin receptor substrates (IRSs) play central roles in insulin/insulin-like growth factor (IGF) signaling and mediate a variety of their bioactivities. IRSs are tyrosine-phosphorylated by activated insulin receptor/IGF-I receptor tyrosine kinase in response to insulin/IGF, and are recognized by signaling molecules possessing the SH2 domain such as phosphatidylinositol 3-kinase (PI3K), leading...